An Open-Label Extension of Study HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase® in Pediatric Patients With Hunter Syndrome and Cognitive Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 9
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This extension study of HGT-HIT-045 is designed to collect long-term safety data in pediatric participants with Hunter syndrome and cognitive impairment who are receiving intrathecal (IT) idursulfase-IT and intravenous (IV) Elaprase enzyme replacement therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 18 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant must have completed all study requirements and End of study (EOS) assessments for study HGT-HIT-045 (NCT00920647) prior to enrolling in Study HGT-HIT-046 and must have no safety or medical issues that contraindicate participation.
- •The participant's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the participant's parent(s) or legally authorized guardian(s) and the participant's assent, as relevant, must be obtained.
- •The participant has received and tolerated a minimum of 12 months of treatment with weekly IV infusions of Elaprase and has received 80% of the total planned infusions within the last 6 months.
排除标准
- •The participant is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) other than the PORT-A-CATH IDDD within 30 days prior to study enrollment or at any time during the study.
- •The participant is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the investigator.
- •The participant has experienced an adverse reaction to study drug in Study HGT-HIT-045 (NCT00920647) that contraindicates further treatment with intrathecal idursulfase-IT.
- •The participant has a known hypersensitivity to any of the components of idursulfase-IT.
- •The participant has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
- •The participant has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:
- •The participant has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device
- •The participant's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the investigator
- •The participant's drug therapy requires substances known to be incompatible with the materials of construction
- •The participant has a known or suspected local or general infection
- •The participant is at risk of abnormal bleeding due to a medical condition or therapy
- •The participant has one or more spinal abnormalities that could complicate safe implantation or fixation
- •The participant has a functioning CSF shunt device
- •The participant has shown an intolerance to an implanted device
- •An additional exclusion criterion for patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045 (NCT00920647):
- •The participant has an opening CSF pressure upon lumbar puncture that exceeds 30.0 centimeter (cm) water (H2O).
研究组 & 干预措施
Idursulfase-IT 1 milligram (mg)
Participants will receive 1 mg idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once monthly and standard-of-care (SoC) therapy of Elaprase intravenous (IV) infusions.
干预措施: Idursulfase-IT (Drug)
Idursulfase-IT 1 milligram (mg)
Participants will receive 1 mg idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once monthly and standard-of-care (SoC) therapy of Elaprase intravenous (IV) infusions.
干预措施: Elaprase (Drug)
Idursulfase-IT 10 mg
Participants will receive 10 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.
干预措施: Idursulfase-IT (Drug)
Idursulfase-IT 10 mg
Participants will receive 10 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.
干预措施: Elaprase (Drug)
Idursulfase-IT 30 mg
Participants will receive 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.
干预措施: Idursulfase-IT (Drug)
Idursulfase-IT 30 mg
Participants will receive 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.
干预措施: Elaprase (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From start of study drug administration up to follow-up (up to 165 months)
An adverse event (AE) is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, and/or laboratory changes occurring in any phase of a clinical trial, and whether or not considered study drug-related. TEAEs were defined as all AEs occurring on or after the first IDDD surgery date or first dose (whichever is earlier) for the participant (whether it is in this extension study or in HGT HIT-045 \[NCT00920647\]) and before the end of the study (EOS) visit (+30 days). For Idursulfase-IT 1 mg+10 mg arm the summary presented includes only the TEAEs that occurred while the participants were assigned to 10 mg.
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters
时间窗: From start of study drug administration up to follow-up (up to 165 months)
Number of participants with clinically significant changes in laboratory parameters (chemistry, hematology, urinalysis and CSF values) were collected.
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings
时间窗: From start of study drug administration up to follow-up (up to 165 months)
Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) findings (heart rate, PR interval, QRS interval, QT interval and the corrected QT interval) were collected.
CSF Chemistries: Change From Baseline in CSF Total Cell Count
时间窗: Baseline, Month 163
CSF Chemistries: Change From Baseline in CSF Glucose
时间窗: Baseline, Month 163
CSF Chemistries: Change From Baseline in CSF Protein
时间窗: Baseline, Month 163
Number of Participants With Anti-idursulfase Antibodies in CSF
时间窗: From start of study drug administration up to follow-up (up to 165 months)
Number of Participants With Anti-idursulfase Antibodies in Serum
时间窗: From start of study drug administration up to follow-up (up to 165 months)
次要结局
- Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Area Under the Curve From the Time of Dosing to the Last Measureable Concentration (AUC0-t) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Time of Maximum Observed Concentration (Tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (Cl/F) of Idursulfase-IT Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Volume of Distribution Associated With the Terminal Slope Following Extravascular Administration Divided by the Fraction of Dose Absorbed (Vz/F) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase(15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups)
- Total Body Clearance (CL) of Elaprase(15 minutes prior to IV infusion, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 9, 11, and 24 hours during/after the IV infusion on Days 3-7 of Weeks 3 and 23)
- Observed Steady-state Volume of Distribution (Vss) of Elaprase(15 minutes prior to IV infusion and at multiple timepoint (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23)
- Volume of Distribution (Vz) of Elaprase(15 minutes prior to IV infusion and at multiple timepoints (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23)
- Mean Residence Time Extrapolated to Infinity (MRT0-inf) of Elaprase(15 minutes prior to IV infusion and at multiple timepoints (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23)
- Change From Baseline in CSF Biomarkers(Baseline, Months 7, 55, and 139)
- Change From Baseline in Urinary Glycosaminoglycan (GAG)(Baseline, Months 7, 55, and 163)